Redox-responsive core-cross-linked block copolymer micelles for overcoming multidrug resistance in cancer cells

Maiti, Chiranjit ; Parida, Sheetal ; Kayal, Shibayan ; Maiti, Saikat ; Mandal, Mahitosh ; Dhara, Dibakar (2018) Redox-responsive core-cross-linked block copolymer micelles for overcoming multidrug resistance in cancer cells ACS Applied Materials & Interfaces, 10 (6). pp. 5318-5330. ISSN 1944-8244

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Success of chemotherapy as a treatment for cancer has been often inhibited by Multidrug Resistance (MDR) of the cancer cells. There is a clear need to generate strategies to overcome this resistance. In this work, we have developed redox-responsive and core-cross-linked micellar nanocarriers using poly(ethylene glycol)-block-poly(2-(methacryloyloxy)ethyl 5-(1,2-dithiolan-3-yl)pentanoate) diblock copolymers (PEG-b-PLAHEMA) with tunable swelling properties for the delivery of drugs toward drug-sensitive MDA-MB-231 and drug-resistant MDA-MB-231 (231R) cancer cells. PEG-b-PLAHEMA containing varying number of 2-(methacryloyloxy)ethyl 5-(1,2-dithiolan-3-yl)pentanoate (LAHEMA) units were synthesized by employing the reversible addition-fragmentation chain transfer polymerization technique. The block copolymer self-assembly, cross-linking induced by reduction, and de-cross-linking triggered time-dependent controlled swelling of micelles were studied using dynamic light scattering, fluorescence spectroscopy, and transmission electron microscopy. In vitro cytotoxicity, cellular uptake efficiency, and glutathione-responsive anticancer activity of Doxorubicin (DOX) encapsulated in core-Cross-linked block Copolymer Micelles (CCMs) toward both drug-sensitive and drug-resistant cancer cell lines were evaluated. Significant reduction in IC50 was observed by DOX-loaded CCMs toward drug-resistant 231R cancer cell lines, which was further improved by coencapsulating DOX and verapamil (a P-glycoprotein inhibitor) in CCMs. Thus, these reduction-sensitive biocompatible CCMs with tunable swelling property are very promising in overcoming MDR in cancer cells.

Item Type:Article
Source:Copyright of this article belongs to American Chemical Society.
Keywords:Apoptosis; Biocompatible Polymers; Doxorubicin; Drug Delivery; Glutathione; Nanoparticles; RAFT Polymerization; Self-assembly; Stimuli-responsive Polymers; Verapamil
ID Code:113328
Deposited On:08 May 2018 11:12
Last Modified:08 May 2018 11:12

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